Lourdes Rodriguez-de la Rosa

RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors

Background Insulin-like growth factor-I (IGF-I) provides pivotal cell survival and differentiation signals during inner ear development throughout evolution. Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation. In the mouse, deficits in IGF-I result in profound hearing loss associated with reduced survival, differentiation and maturation of auditory neurons. Nevertheless, little is known about the molecular basis of IGF-I activity in hearing and deafness. Methodology/Principal Findings A combination of quantitative RT-PCR, subcellular fractionation and Western blotting, along with in situ hybridization studies show IGF-I and its high affinity receptor to be strongly expressed in the embryonic and postnatal mouse cochlea. The expression of both proteins decreases after birth and in the cochlea of E18.5 embryonic Igf1−/− null mice, the balance of the main IGF related signalling pathways is altered, with lower activation of Akt and ERK1/2 and stronger activation of p38 kinase. By comparing the Igf1−/− and Igf1+/+ transcriptomes in E18.5 mouse cochleae using RNA microchips and validating their results, we demonstrate the up-regulation of the FoxM1 transcription factor and the misexpression of the neural progenitor transcription factors Six6 and Mash1 associated with the loss of IGF-I. Parallel, in silico promoter analysis of the genes modulated in conjunction with the loss of IGF-I revealed the possible involvement of MEF2 in cochlear development. E18.5 Igf1+/+ mouse auditory ganglion neurons showed intense MEF2A and MEF2D nuclear staining and MEF2A was also evident in the organ of Corti. At P15, MEF2A and MEF2D expression were shown in neurons and sensory cells. In the absence of IGF-I, nuclear levels of MEF2 were diminished, indicating less transcriptional MEF2 activity. By contrast, there was an increase in the nuclear accumulation of FoxM1 and a corresponding decrease in the nuclear cyclin-dependent kinase inhibitor p27Kip1. Conclusions/Significance We have defined the spatiotemporal expression of elements involved in IGF signalling during inner ear development and reveal novel regulatory mechanisms that are modulated by IGF-I in promoting sensory cell and neural survival and differentiation. These data will help us to understand the molecular bases of human sensorineural deafness associated to deficits in IGF-I.

The role of insulin-like growth factor-I in the physiopathology of hearing

Insulin-like growth factor-I (IGF-I) belongs to the family of polypeptides of insulin, which play a central role in embryonic development and adult nervous system homeostasis by endocrine, autocrine, and paracrine mechanisms. IGF-I is fundamental for the regulation of cochlear development, growth, and differentiation, and its mutations are associated with hearing loss in mice and men. Low levels of IGF-I have been shown to correlate with different human syndromes showing hearing loss and with presbyacusis. Animal models are fundamental to understand the genetic, epigenetic, and environmental factors that contribute to human hearing loss. In the mouse, IGF-I serum levels decrease with aging and there is a concomitant hearing loss and retinal degeneration. In the Igf1−/− null mouse, hearing loss is due to neuronal loss, poor innervation of the sensory hair cells, and age-related stria vascularis alterations. In the inner ear, IGF-I actions are mediated by intracellular signaling networks, RAF, AKT, and p38 MAPK protein kinases modulate the expression and activity of transcription factors, as AP1, MEF2, FoxM1, and FoxP3, leading to the regulation of cell cycle and metabolism. Therapy with rhIGF-I has been approved in humans for the treatment of poor linear growth and certain neurodegenerative diseases. This review will discuss these findings and their implications in new IGF-I-based treatments for the protection or repair of hearing loss.

Insulin receptor substrate 2 (IRS2)-deficient mice show sensorineural hearing loss that is delayed by concomitant protein tyrosine phosphatase 1B (PTP1B) loss of function

The insulin receptor substrate (IRS) proteins are key mediators of insulin and insulinlike growth factor 1 (IGF-1) signaling. Protein tyrosine phosphatase (PTP)-1B dephosphorylates and inactivates both insulin and IGF-1 receptors. IRS2-deficient mice present altered hepatic insulin signaling and β-cell failure and develop type 2-like diabetes. In addition, IRS2 deficiency leads to developmental defects in the nervous system. IGF1 gene mutations cause syndromic sensorineural hearing loss in humans and mice. However, the involvement of IRS2 and PTP1B, two IGF-1 downstream signaling mediators, in hearing onset and loss has not been studied. Our objective was to study the hearing function and cochlear morphology of Irs2-null mice and the impact of PTP1B deficiency. We have studied the auditory brainstem responses and the cochlear morphology of systemic Irs2−/−Ptpn1+/+, Irs2+/+Ptpn1−/− and Irs2−/−Ptpn1−/− mice at different postnatal ages. The results indicated that Irs2−/−Ptpn1+/+ mice present a profound congenital sensorineural deafness before the onset of diabetes and altered cochlear morphology with hypoinnervation of the cochlear ganglion and aberrant stria vascularis, compared with wild-type mice. Simultaneous PTP1B deficiency in Irs2−/−Ptpn1−/− mice delays the onset of deafness. We show for the first time that IRS2 is essential for hearing and that PTP1B inhibition may be useful for treating deafness associated with hyperglycemia and type 2 diabetes.

Treatment with N- and C-Terminal Peptides of Parathyroid Hormone-Related Protein Partly Compensate the Skeletal Abnormalities in IGF-I Deficient Mice

Insulin-like growth factor-I (IGF-I) deficiency causes growth delay, and IGF-I has been shown to partially mediate bone anabolism by parathyroid hormone (PTH). PTH-related protein (PTHrP) is abundant in bone, and has osteogenic features by poorly defined mechanisms. We here examined the capacity of PTHrP (1–36) and PTHrP (107–111) (osteostatin) to reverse the skeletal alterations associated with IGF-I deficiency. Igf1-null mice and their wild type littermates were treated with each PTHrP peptide (80 µg/Kg/every other day/2 weeks; 2 males and 4 females for each genotype) or saline vehicle (3 males and 3 females for each genotype). We found that treatment with either PTHrP peptide ameliorated trabecular structure in the femur in both genotypes. However, these peptides were ineffective in normalizing the altered cortical structure at this bone site in Igf1-null mice. An aberrant gene expression of factors associated with osteoblast differentiation and function, namely runx2, osteoprotegerin/receptor activator of NF-κB ligand ratio, Wnt3a , cyclin D1, connexin 43, catalase and Gadd45, as well as in osteocyte sclerostin, was found in the long bones of Igf1-null mice. These mice also displayed a lower amount of trabecular osteoblasts and osteoclasts in the tibial metaphysis than those in wild type mice. These alterations in Igf1-null mice were only partially corrected by each PTHrP peptide treatment. The skeletal expression of Igf2, Igf1 receptor and Irs2 was increased in Igf1-null mice, and this compensatory profile was further improved by treatment with each PTHrP peptide related to ERK1/2 and FoxM1 activation. In vitro, PTHrP (1–36) and osteostatin were effective in promoting bone marrow stromal cell mineralization in normal mice but not in IGF-I-deficient mice. Collectively, these findings indicate that PTHrP (1–36) and osteostatin can exert several osteogenic actions even in the absence of IGF-I in the mouse bone.

Age-regulated function of autophagy in the mouse inner ear.

Autophagy is a highly conserved catabolic process essential for embryonic development and adult homeostasis. The autophagic machinery supplies energy by recycling intracellular components and facilitates the removal of apoptotic cells. In the inner ear, autophagy has been reported to play roles during early development in the chicken embryo and in the response to otic injury in the adult mouse. However, there are no studies on the expression of the autophagy machinery in the postnatal and adult inner ear. Insulin-like growth factor 1 (IGF-1) is one of the factors that regulate both otic development and cochlear postnatal maturation and function. Here, we hypothesised that autophagy could be one of the processes involved in the cochlear development and functional maturation. We report that autophagy-related genes (ATG) Becn1, Atg4g and Atg5 are expressed in the mouse cochlea, vestibular system and brainstem cochlear nuclei from late developmental stages to adulthood. Atg9 was studied in the mouse cochlea and showed a similar pattern. The presence of autophagic flux was confirmed by decreased sequestosome 1 (SQSTM1/p62) and increased relative levels of microtubule-associated protein light chain 3-II (LC3-II). Inner ear autophagy flux is developmentally regulated and is lower at perinatal stages than in the adult mouse, where an expression plateau is reached at the age of two-months, coinciding with the age at which full functional activity is reached. Expression is maintained in adult mice and declines after the age of twelve months. LC3B labelling showed that autophagy was primarily associated with spiral ganglion neurons. Over time, Igf1 wild type mice showed lower expression of genes coding for IGF-1 high affinity receptor and the family factor IGF-2 than null mice. Parallel analysis of autophagy machinery gene expression showed no significant differences between the genotypes over the lifespan of the null mice. Taken together, these results show that the autophagy machinery expression in the inner ear is regulated with age but is not compromised by the chronic absence of IGF-1. Our data also strongly support that the up-regulation of autophagy machinery genes is concomitant with the functional maturation of the inner ear.

Autophagy resolves early retinal inflammation in Igf1-deficient mice

ABSTRACT Insulin-like growth factor-1 (IGF-1) is a growth factor with differentiating, anti-apoptotic and metabolic functions in the periphery, and anti-inflammatory properties in the nervous system. Mice that have mutations in the Igf1 gene, rendering the gene product inactive (Igf1−/−), present with age-related visual loss accompanied by structural alterations in the first synapses of the retinal pathway. Recent advances have revealed a crucial role of autophagy in immunity and inflammation. Keeping in mind this close relationship, we aimed to decipher these processes in the context of the defects that occur during ageing in the retina of Igf1−/− mice. Tnfa and Il1b mRNAs, and phosphorylation of JNK and p38 MAPK were elevated in the retinas of 6- and 12-month old Igf1−/− mice compared to those in age-matched Igf1+/+ controls. In 6-month-old Igf1−/− retinas, increased mRNA levels of the autophagy mediators Becn1, Atg9, Atg5 and Atg4, decreased p62 (also known as SQSTM1) protein expression together with an increased LC3-II:LC3-I ratio reflected active autophagic flux. However, in retinas from 12-month-old Igf1−/− mice, Nlrp3 mRNA, processing of the IL1β pro-form and immunostaining of active caspase-1 were elevated compared to those in age-matched Igf1+/+ controls, suggesting activation of the inflammasome. This effect concurred with accumulation of autophagosomes and decreased autophagic flux in the retina. Microglia localization and status of activation in the retinas of 12-month-old Igf1+/+ and Igf1−/− mice, analyzed by immunostaining of Cd11b and Iba-1, showed a specific distribution pattern in the outer plexiform layer (OPL), inner plexiform layer (IPL) and inner nuclear layer (INL), and revealed an increased number of activated microglia cells in the retina of 12-month-old blind Igf1−/− mice. Moreover, reactive gliosis was exclusively detected in the retinas from 12-month-old blind Igf1−/− mice. In conclusion, this study provides new evidence in a mouse model of IGF-1 deficiency that autophagy is an adaptive response that might confer protection against persistent inflammation in the retina during ageing. Summary: Igf1-deficient mice show chronic inflammation in the retina, and we reveal that controlling inflammation through autophagy in young mice could prevent loss of retinal function.

Comparative gene expression study of the vestibular organ of the Igf1 deficient mouse using whole-transcript arrays.

The auditory and vestibular organs form the inner ear and have a common developmental origin. Insulin like growth factor 1 (IGF-1) has a central role in the development of the cochlea and maintenance of hearing. Its deficiency causes sensorineural hearing loss in man and mice. During chicken early development, IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system. In this study we have compared the whole transcriptome of the vestibular organ from wild type and Igf1(-/-) mice at different developmental and postnatal times. RNA was prepared from E18.5, P15 and P90 vestibular organs of Igf1(-/-) and Igf1(+/+) mice and the transcriptome analysed in triplicates using Affymetrix(®) Mouse Gene 1.1 ST Array Plates. These plates are whole-transcript arrays that include probes to measure both messenger (mRNA) and long intergenic non-coding RNA transcripts (lincRNA), with a coverage of over 28 thousand coding transcripts and over 7 thousands non-coding transcripts. Given the complexity of the data we used two different methods VSN-RMA and mmBGX to analyse and compare the data. This is to better evaluate the number of false positives and to quantify uncertainty of low signals. We identified a number of differentially expressed genes that we described using functional analysis and validated using RT-qPCR. The morphology of the vestibular organ did not show differences between genotypes and no evident alterations were observed in the vestibular sensory areas of the null mice. However, well-defined cellular alterations were found in the vestibular neurons with respect their number and size. Although these mice did not show a dramatic vestibular phenotype, we conducted a functional analysis on differentially expressed genes between genotypes and across time. This was with the aim to identify new pathways that are involved in the development of the vestibular organ as well as pathways that maybe affected by the lack of IGF-1 and be associated to the morphological changes of the vestibular neurons that we observed in the Igf1(-/-) mice.

Cellular models to study sensorineural hearing loss caused by IGF-1 deficiency

Tesis llevada a cabo para conseguir el grado de Doctor por la Universidad de Complutense de Madrid.--2018-01-15.--Sobresaliente cum laudeContiene 7 documentos (1. Objetivos, alcance y publicaciones. 2. Registro y codigo) y 5 con el softwareespanolLas ciber amenazas afectan a todo tipo de organizaciones, causando frecuentes y costosos impactos globalmente. Recientemente, han surgido productos de ciberseguro con el potencial de reducir el impacto de los riesgos en el ciberespacio. Sin embargo, aun tienen que madurar. En este articulo presentamos varios modelos de analisis de riesgos que podrian facilitar la implantacion y adopcion de ciberseguros. Estos modelos, descritos como diagramas de influencia y diagramas de influencia bi-agente, aportan un marco para estimar el impacto economico de los ciber riesgos a los que se enfrentan aseguradores y asegurados, asi como tambien para calcular sus estrategias optimas de mitigacion y transferencia del riesgo. EnglishCyber threats affect all kinds of organisations with frequent and costly impacts worldwide. Cyber insurance products have recently emerged with the potential of lowering the impact of cyberspace risks. However, they have yet to mature. In this paper we present several risk analysis models that may facilitate the implementation and adoption of cyber insurance. These models, described in terms of influence diagrams and bi-agent influence diagrams, provide a framework for estimating the economic impact of cyber risks that may face insurers and insurees as well as calculating their optimal risk mitigation and transfer strategies.Trabajo presentado a la III Iberoamerican Conference on Supercritical Fluids celebrada en Cartagena de Indias (Colombia) del 1 al 5 de abril de 2013.Trabajo presentado a la 26th IAEA Fusion Energy Conference, celebrada en Kyoto (Japon) del 17 al 22 de octubre de 2016.The Joint Iberian Meeting on Atomic and Molecular Physics (IBER), Barcelona, September 12-14th, 2017. -- http://iber2017.com/index.phpPoster presentado en el 10o Congreso de la Asociacion Iberica de Endocrinologia Comparada AIEC, celebrado en Castellon, Espana, del 23 al 25 de septiembre de 2015Resumen del trabajo presentado a la XI Reunion del Grupo de Microbiologia Molecular, celebrada en Sevilla del 6 al 8 de septiembre de 2016.Chinchilla-Rodriguez, Zaida; Miguel, Sandra; Perianes-Rodriguez, Antonio; Ovalle-Perandones, Antonia; Olmeda-Gomez, Carlos. (2016). Autonomy vs. dependency of scientific collaboration in scientific performance . 21st International Conference on Science and Technology Indicators, STI2016. Valencia, Spain, 14-16 September 2016XXV National Spectroscopy Meeting (XXV RNE), IX Iberian Spectroscopy Conference (IX CIE), Alicante, 20th-22nd July, 2016Resumen del trabajo presentado a la 43rd International Conference on Micro and Nano Engineering (MNE), celebrada en Braga (Portugal) del 18 al 22 de septiembre de 2017.Contiene 7 documentos (1. Objetivos, alcance y publicaciones. 2. Registro, interface y codigo) y 5 con el softwarePoster presentado en el congreso 4th SCARCE International Conference, celebrado en Cadiz, Espana el 25 y 26 de noviembre de 2013We present a Cultural Heritage conceptual data model built under the European INSPIRE ( Infrastructure for Spatial Information in the European Community ) Directive. Our model develops the Data Specification on Protected Sites , part of the INSPIRE Annex I. Hence its orientation towards georeferenced heritage data. The data model has been developed by an interdisciplinary group made up of specialists in the field of Geomatics and Cultural Heritage. It is our aim to achieve a generic, extendable and interoperable schema. It should be generic enough to embrace all kind of protected heritage data, from an ancient pilgrim’s way to the last artifact found in an archaeological excavation, extendable to allow any kind of data producer to adapt the model to the nature of their own information and interoperable to combine spatial data sets from different sources through network services, via Internet. The achievement of these three characteristics features international norms and standards referred to our kind of data. This implies adaptation to INSPIRE as well as to several ISO norms: ISO 19100 series regarding geographical information, ISO 21127 (CIDOC-CRM Model) for heritage thematic data and ISO 15836 (Dublin Core) for document resources. The data model comprehends two main dimensions: cultural entities in a strict sense, and the legislative figures created to protect them. This allows for the representation of cultural objects (i.e. historical buildings or archaeological sites) and their link to their legislative protection, keeping them as separate realities. In order to describe the data model, an international common language has been used: UML (Unified Modeling Language), a standard itself. Thus, we present a class-diagram depicting all legal and cultural entities, in the form of classes with their corresponding relations, attributes, constraints and stereotypes.Trabajo presentado en el 11th Spanish-Italian Symposium on Organic Chemistry SISOC-XI celebrado en San Sebastian (Espana), del 13 al 15 de julio de 2016.Trabajo presentado en el XVIII Congreso Peruano de Geologia, celebrado en Lima (Peru), del 16 al 19 de octubre de 2016Poster presentado en las XXXIII Jornadas de la Asociacion Espanola de Entomologia, celebradas en Almeria, del 15 al 18 de noviembre de 2017This research has been funded by the Spanish Ministry of Economy and Competitiveness, through research projects POSTFIRE (CGL2013-47862-C2-1-R) and GEOFIRE (CGL2012-38655-C04-01)The main contribution of this work is the improvement of the efficiency of a PEMFC power system while guaranteeing conditions that also improve its durability. Adopting the NMPC scheme with the distributed parameter model and the nonlinear observer, the efficiency of the PEMFC-based system can be maximized guaranteeing at the same time the appropriate internal gas concentration profiles to avoid global and local hydrogen and oxygen starvation and proper membrane humidification.Trabajo presentado en la 13a Reunion de la Red Espanola de Bacterias Lacticas (RedBAL), celebrada en Madrid (Espana) del 17 al 18 de junio de 2019Memoria de tesis doctoral presentada por Uxue Tilves Matheu para obtener el titulo de Doctora en Ciencias del Mar por la Universitat Politecnica de Catalunya (UPC), realizada bajo la direccion de la Dra. Ana Maria Sabates Freijo y de la Dra. Veronica Lorena Fuentes del Institut de Ciencies del Mar (ICM-CSIC).-- 149 pages, appendicesTrabajo presentado por Nuria Vallverdu Coll para la obtencion del grado de Master universitario en investigacion basica y aplicada en recursos cinegeticos, realizado en el Instituto de Investigacion en Recursos Cinegeticos (IREC, CSIC-UCLM-JCCM).Resumen del poster presentado a la 7th International Conference on Polyphenols and Health, celebrada en Tours (Francia) del 27 al 30 de octubre de 2015.Trabajo financiado con el Proyecto DR3AMCGL2014-55118 del MINECO (Proyecto coordinado del proyecto SALTACRES).Trabajo presentado en el Congreso Iberoamericano de Hidrogeno y Pilas de Combustible, celebrado en Barcelona (Espana) del 15 al 17 de octubre de 2014.El presente articulo describe el empleo del flujo de diseno basado en modelos para el desarrollo de bloques reconfigurables automaticamente para el procesado de imagenes sobre FPGA. Para ello se han concebido arquitecturas hardware que aprovechan caracteristicas especificas de algunos algoritmos de procesado y que pueden ser modificadas a traves de un novedoso procedimiento software. Este aspecto, unido a las restantes opciones de parametrizacion de los diferentes modulos, permite liberar al disenador de los detalles especificos de las implementaciones hardware asi como adaptar el consumo de recursos del FPGA a las necesidades de la aplicacion. El proceso de reconfiguracion automatica se ilustra con el bloque de convolucion generico realizando comparaciones entre implementaciones de diferentes arquitecturas sobre un FPGA Spartan-6 LX45.Trabajo presentado en el 8th European Meeting on Solar Chemistry and Photocatalysis, celebrado en Salonica (Grecia) del 25 al 28 de Junio de 2014.Resumen del poster presentado a las I Jornadas Cientificas del CIAL celebradas el 5 de junio de 2014 en Madrid.-- et al.Trabajo presentado en el 4th International Conodont Symposium, celebrado en Valencia (Espana), del 25 al 30 de junio de 2017Comunicacion presentada en el Aquaculture Europe 2014, celebrado en Donostia-San Sebastian, Espana, del 14 al 17 de octubre de 2014Triptico de la reunion celebrada en la Universidad de Murcia del 12 al 14 de Noviembre de 2015.Trabajo presentado en la 11a Reunion de la Red Espanola de Bacterias Lacticas (RedBAL), celebrada en Gijon (Asturias, Espana) del 28 al 30 de Junio de 2017Trabajo Fin de Master: Master en Catalisis Homogenea y Quimica Molecular. Grupo de Cristales liquidos y Polimeros, Departamento de Quimica Organica de la Universidad de Zaragoza (Curso 2014/2015).La elaboracion de este articulo se inscribe en el proyecto de investigacion “Innovacion oculta: cambio de paradigma en los estudios de innovacion” (FFI2011-25475), Ministerio de Economia y Competitividad, Gobierno de Espana.Poster presented at the 18th International Microscopy Congress (ICM 2014) that took place in Prague (Czech Republic) during 7-12th September 2014.Esta investigacion ha sido posible gracias a la financiacion de los proyectos del Plan Nacional CGL2012-36682 y CGL2016-75109-P del Ministerio de Economia y Competitividad, y al Convenio Principado de Asturias-Universidad de Oviedo y MNCN-CSIC.Resumen del poster presentado a la 10th International Conference one Carbon Metabolism, vitamins B and Homocysteine, celebrada en Nancy (Francia) del 7 al 11 de julio de 2015.La celulosa es la fuente de energia mas abundante que hay en la Tierra. Su transformacion en glucosa se considera la etapa mas importante en la produccion de biocombustibles a partir de biomasa lignocelulosica. Para esta transformacion es necesaria la accion sinergica de tres tipos de enzimas que hidrolizan los enlaces s-1,4 de la celulosa: (i) las endoglucanasas, que actuan al azar sobre enlaces internos, (ii) las celobiohidrolasas, que operan progresivamente por los extremos reductores y no reductores de la cadena, y (iii) las s-glucosidasas (BGL), que hidrolizan celobiosa y los celooligosacaridos mas pequenos hasta glucosa. Los hongos filamentosos son la principal fuente de celulasas, siendo los crudos del genero Trichoderma los mas estudiados y comercializados historicamente. Sin embargo, estos hongos secretan niveles insuficientes de BGL para una conversion efectiva de la celulosa, por lo que con frecuencia requieren ser suplementados con preparaciones ricas en esta enzima procedentes de otros hongos. Recientemente, se han descrito cepas de Penicillium con gran capacidad para secretar altos niveles de BGL al medio extracelular. Ademas de su papel en la hidrolisis de la celulosa las BGL tambien pueden emplearse para sintetizar compuestos de interes industrial mediante reacciones de transglicosilacion. En este trabajo se ha estudiado una nueva cepa fungica productora de celulasas, identificada como Talaromyces amestolkiae, en base a un analisis molecular y morfologico. Se han purificado a homogeneidad electroforetica tres BGL (BGL-1, BGL-2 y BGL-3) secretadas por el hongo y se han caracterizado bioquimicamente. BGL-1 y BGL-2 son proteinas monomericas, mientras que BGL-3 es un dimero funcional. Los valores de actividad maxima de estas enzimas se obtuvieron a pH 4,0 y entre 50-60 oC, siendo estables en un rango de pH de 4-7 y a 50 oC. Las tres mostraron distinto comportamiento en funcion del sustrato (pNPG o celobiosa), ensayandose tambien el efecto de determinados compuestos quimicos e inhibidores en su actividad. Las tres pueden hidrolizar celooligosacaridos de diferente longitud, disminuyendo la eficacia de hidrolisis con el aumento de la polimerizacion, y no son activas frente a polisacaridos. Ademas, mostraron actividad de transglicosilacion, formando alquilglicosidos y celooligosacaridos de mayor longitud que los usados como sustratos. Las tres BGL se identificaron mediante huella peptidica y en base la alta homologia con otras BGL fungicas relacionadas filogeneticamente, se disenaron cebadores especificos que permitieron la secuenciacion de los genes que codifican cada una de ellas. El analisis de las secuencias aminoacidicas mostro que BGL-1 es miembro de la familia 1 de las glicosil hidrolasas, mientras que BGL-2 y BGL-3 pertenecen a la familia 3. Teniendo en cuenta que existen pocas BGL fungicas cristalizadas, se construyeron modelos moleculares de estas ultimas en base a las estructuras con las que presentaron mayor identidad. El crudo enzimatico de T. amestolkiae, rico en BGL, se uso de forma individual y como suplemento de otros cocteles comerciales en experimentos de sacarificacion a partir de slurry acido de paja de trigo. Los resultados obtenidos indican que el hongo secreta, ademas de celulasas, otras enzimas complementarias que potencian la liberacion de azucares fermentables. Se analizo el secretoma de T. amestolkiae usando Avicel o slurry acido de paja de trigo como fuente de carbono. Las celulasas fueron las enzimas mas abundantes en ambas condiciones, sin embargo, en el crudo obtenido a partir de los cultivos en slurry aumento la proporcion de BGL y otras enzimas distintas a las celulasas, indicando que para la degradacion de un sustrato complejo es necesaria mayor diversidad enzimatica. Los resultados obtenidos en este trabajo abren nuevas vias para la formulacion de cocteles enzimaticos eficaces en el contexto de la degradacion de la biomasa lignocelulosica.Trabajo presentado en el 4th International Congress on Ichnology - ICHNIA 2016: Ichnology for the 21st century: (Palaeo) Biological Traces towards Sustainable Development, celebrado en Idanha-a-Nova (Portugal), del 6 al 9 de mayo de 2016Resumen del trabajo presentado al Joint European Magnetic Symposia (JEMS), celebrado en Glasgow (UK) del 21 al 26 de agosto de 2016.Vazquez, J. T. ... et. al.-- Inciativa Iberica para el Estudio de las Fallas Activas, Tercera Reunion Iberica sobre Fallas Activas y Paleosismologia IBERFAULT 2018 - Third Iberian Meeting on Active Faults and Paleoseismology, 11-13 June 2018, Alicante, Spain.-- 4 pages, 2 figuresLa infeccion temprana por Verticillium dahliae en olivar y la discriminacion entre niveles de severidad de la Verticilosis es viable mediante la utilizacion de imagenes termicas, multiespectrales e hiperespectrales adquiridas con vehiculos aereos no tripulados a escala de parcela o tripulados a escala de comarca. El indicador relacionado con la temperatura de copa (CWSI), indices de reflectancia (B, BG1, BR1) y la fluorescencia clorofilica (FLD3) se identifican como buenos indicadores para detectar la Verticilosis en etapas tempranas del desarrollo de la enfermedad, mientras que NDVI, PRI515, R/G, HI e indices de estimacion de clorofila y carotenos demuestran ser buenos indicadores para la cuantificacion de dano moderado o severo causada por Verticilosis, lo que puede ser de utilidad para el diseno de estrategias de control de la Verticilosis a escala de parcela y de comarca. La infeccion temprana por Verticillium dahliae en olivar y la discriminacion entre niveles de severidad de la Verticilosis es viable mediante la utilizacion de imagenes termicas, multiespectrales e hiperespectrales adquiridas con vehiculos aereos no tripulados a escala de parcela o tripulados a escala de comarca. El indicador relacionado con la temperatura de copa (CWSI), indices de reflectancia (B, BG1, BR1) y la fluorescencia clorofilica (FLD3) se identifican como buenos indicadores para detectar la Verticilosis en etapas tempranas del desarrollo de la enfermedad, mientras que NDVI, PRI515, R/G, HI e indices de estimacion de clorofila y carotenos demuestran ser buenos indicadores para la cuantificacion de dano moderado o severo causada por Verticilosis, lo que puede ser de utilidad para el diseno de estrategias de control de la Verticilosis a escala de parcela y de comarca. El olivo (Olea europaea L.) es el cultivo lenoso no tropical que ocupa mayor superficie en todo el mundo, con el 95% de la produccion mundial localizada en la cuenca mediterranea. Espana es el pais con mayor superficie de olivar del mundo con 2,6 MHa y aproximadamente el 39% de la produccion mundial. La Verticilosis, causada por el hongo de suelo Verticillium dahliae Kleb, constituye la principal amenaza para el olivar. Esta enfermedad afecta al olivo en todos los paises de tradicion olivarera y causa importantes perdidas de rendimiento y muerte de los arboles (Jimenez-Diaz y col., 2012). Este patogeno coloniza el sistema vascular de la planta, bloqueando el flujo del agua y finalmente induciendo estres hidrico (Van Alfen, 1989).Espana es el mayor productor de citricos de la Union Europea y el quinto a nivel mundial, con una produccion anual superior a cinco millones de toneladas (MAGRAMA, 2016). Este sector genera una gran cantidad de subproductos, con un elevado aporte energetico y alto contenido en pectinas y azucares, por lo que podrian usarse como materias primas en dietas para rumiantes. Sin embargo, los subproductos de citricos son muy diversos, por lo que su composicion quimica y valor nutritivo tambien puede ser variable (FEDNA, 2010; Feedipedia, 2016). El objetivo de este trabajo fue analizar la composicion quimica y la produccion de gas in vitro de subproductos de citricos producidos en nuestro pais.Resumen del trabajo presentado a las I Jornadas Cientificas del CIAL celebradas el 5 de junio de 2014 en Madrid.The Indian Summer Monsoon onset is one of the meteorological events most anticipated in the world. Due to its relevance for the population, the India Meteorological Department has dated the onset over the southern tip of the Indian Peninsula (Kerala) since 1901. The traditional method to date the onset was based in the judgment of skilled meteorologist and because of this, the method was considered subjective and not adequate for the study of long-term changes in the onset.Resumen del poster presentado a las I Jornadas Cientificas del CIAL celebradas el 5 de junio de 2014 en Madrid.Trabajo presentado en el European Workshop on Experimental and Behavioral Economics (EWEBE), organizado por la Universidad de Bologna los dias 26 y 27 de mayo de 2017 con el titulo: The impact of deliberative structures on voting behavio.--Trabajo presentado en los Bilkent Microeconomics Seminars organizados por la Bilkent University (Ankara, Turkey) el dia 29 de noviembre de 2017La compacidad del racimo es un rasgo de gran interes en la vid, dado que puede condicionar su calidad y rendimiento. Estos efectos se producen fundamentalmente a traves de su relacion, directa o indirecta, con la arquitectura del racimo, el comportamiento reproductivo y el grado o modo de exposicion de las bayas al ambiente. Respecto a los dos primeros, en un estudio previo, determinamos que tanto la longitud del raquis y sus primeras ramas como el numero de bayas por racimo son los caracteres con mayor incidencia en la compacidad entre los analizados. Ahora bien, el estudio de la base genetica responsable del numero de bayas requiere de su diseccion previa, dado que es una variable secundaria, resultado del numero de flores por inflorescencia y de la tasa de cuajado o conversion de flor en fruto. En este trabajo se presenta un estudio preliminar en el que se han caracterizado fenotipicamente 104 variedades de vid para estudiar su comportamiento reproductivo. Asi, sobre una base amplia de diversidad varietal, se han estimado variables como el numero de flores, la tasa de cuajado, corrimiento, millerandage, etc., evaluando su posible relacion con la compacidad del racimo. Este trabajo, una vez completado durante varios anos, permitira conocer la diversidad existente para el comportamiento reproductivo en la vid, asi como, de forma mas concreta, abordar la caracterizacion de los procesos geneticos responsables de las diferencias fenotipicas detectadas para el comportamiento reproductivo y sus elementos individuales y para la compacidad del racimo, identificando los posibles genes involucrados en dichos procesos.Trabajo presentado en la 11th International Conference on Grapevine Breeding and Genetics, celebrada en Pekin del 29 de julio al 2 de agosto de 2014.The Polarimetric and Helioseismic Imager (PHI) is the first deep-space solar spectropolarimeter, on-board the Solar Orbiter (SO) space mission. It faces: stringent requirements on science data accuracy, a dynamic environment, and severe limitations on telemetry volume. SO/PHI overcomes these restrictions through on-board instrument calibration and science data reduction, using dedicated firmware in FPGAs. This contribution analyses the accuracy of a data processing pipeline by comparing the results obtained with SO/PHI hardware to a reference from a ground computer. The results show that for the analysed pipeline the error introduced by the firmware implementation is well below the requirements of SO/PHI.This work has been financed within the framework of the projects P/309307 Arqueoastronomia of the IAC, and Orientatio ad sidera III (AYA2011-26759) of the Spanish MINECO. ACGG is Ramon y Cajal researcher of the MINECO.Este trabajo ha sido financiado por el proyecto RECUPERA 2020 del MINECO y EU-FEDER; y por el proyecto TRANS·FORMA (PP.TRA.TAA201600.9). La investigacion realizada por E. Rodriguez ha sido realizada gracias al programa DOC-INIA (INIA-FEDER).Trabajo presentado en el XXIV Congreso Iberoamericano de Catalisis (CICat 2014), “Catalisis para Biorrefineria”, celebrado en Medellin del 11 al 13 de septiembre de 2014.2 paginas y 1 tabla.- Trabajo presentado en el IX Congreso de Mejora Genetica de Plantas celebrado en Murcia entre el 18 y el 20 de septiembre de 2018.3 paginas, 1 tabla, 1 figura.--Trabajo presentado a las XVI Jornadas sobre Produccion Animal AIDA (Zaragoza, 19 al 20 de mayo, 2015).Poster presentado en el XVI International Clay Conference from the Oceans to Space Granada, Spain, July 17-21, (2017)XIII Reunion Iberica de Algas Toxicas y Biotoxinas Marinas (REDIBAL 2018) - XIII Reunion Iberica de Fitoplancton Toxico - XIII Iberian Toxic Algae and Marine Biotoxins Meeting, VI Simposio Internacional de Ciencias del Mar - VI International Symposium of Marine Sciences (ISMS 2018), 20- 22 June 2018, Vigo.-- 2 pagesThis research was financed with project AGL2011-22783 granted by the Spanish Ministry of Economy and Competiveness. M.C. Soto was supported by a CONACYT (Mexican Council of Sciences and Technology) doctoral fellowship.This work was supported by the Spanish Ministerio de Economia y Competitividad (grants CGL2012-36251 and CGL2015-64727-P to X.B., and BFU2010-15906 to JLM), and Catalan Government (2014 SGR 619). The research has also benefited from FEDER funds.Trabajo presentado en el IX International Symposium on Grapevine Physiology and Biotechnology, celebrado en La Serena (Chile) del 21 al 26 de abril de 2013.5 paginas, 4 figuras, 1 tabla.--Trabajo presentado a las: XLI Jornadas Cientificas y XVII Jornadas Internacionales de Ovinotecnia y Caprinotecnia. (Talavera de la Reina, Toledo, Espana, 14-16 septiembre, 2016).Se presenta una revisión histórica de los equinodermos Ordovícicos de Portugal. Todos los registros conocidos hasta el momento pertenecen al Ordovícico Medio-Superior (Darriwiliense-Katiense) y las asociaciones presentan gran diversidad aunque en general los taxones están poco o mal conocidos. La mayor parte de los yacimientos se concentran en las regiones de Amêndoa-Mação y Buçaco, aunque también existen citas de equinodermos en Arouca, Dornes, Moncorvo y Valongo. Por último se comentan futuras líneas de trabajo que ayudarán a comprender mejor estas faunas, perfeccionar y completar el conocimiento del registro fósil del grupo en el Ordovícico centroibérico. Ordovician echinoderms from Portugal: state of the artResumen del trabajo presentado al 37o Convegno Internazionale dei Docenti della Rappresentazione de la Unione Italiana Disegno (UDI), celebrado en Torino (Italia) del 17 al 19 de septiembre de 2015.Trabajo presentado al Danish Days on Caloric Materials and Devices, celebrado en Roskilde (Dinamarca) del 2 al 3 de octubre de 2017.Trabajo presentado en el ImageNano 2015 (Bringing together Nanoscience and Nanotechnology), celebrado en Bilbao del 10 al 13 de marzo de 2015.Este estudio ha sido financiado por el proyecto AGL-2012-40172-C02-01 del Ministerio de Economia y Competitividad (MINECO). AEF agradece al MINECO la financiacion de su contrato de investigacion (FPI).We present a detailed study of a X -ray selected sample of 5 submillimeter bright QSOs at

The Role of Insulin-Like Growth Factor 1 in the Progression of Age-Related Hearing Loss

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Igf1 haploinsufficiency accelerates age-related hearing loss and increases noise-induced cochlear injury

, where the highest rates of star formation (SF) and further growth of black holes (BH) occur. Therefore, this sample is a great laboratory to investigate the co-evolution of star formation and AGN. We present here the analysis of the spectral energy distributions (SED) of the 5 QSOS, including new data from Herschel PACS and SPIRE. Both AGN components (direct and reprocessed) and like Star Formation (SF) are needed to model its SED. From the SED and their UV-optical spectra we have estimated the mass of the black hole (